Rituximab was no better than azathioprine for keeping EGPA in remission

A twice-yearly infusion of the B-cell drug rituximab did no better than a daily azathioprine tablet at keeping a rare eosinophilic vasculitis in remission, in a French randomised trial that set out to prove rituximab superior and found it was not [s1]. The result pushes back on the assumption that the newer, more expensive biologic must be the stronger maintenance option.

Eosinophilic granulomatosis with polyangiitis (EGPA) is an uncommon autoimmune disease in which an overactive immune response inflames small blood vessels, often alongside severe asthma and chronic sinus disease. Treatment first drives the disease into remission — usually with high-dose steroids and other immune-suppressing drugs — and then tries to keep it there while tapering steroids down, because long-term steroids carry their own heavy toll. Guidelines recommend considering maintenance therapy once remission is reached, but there has been little head-to-head evidence on which maintenance drug to choose [s1].

What the trial did

The MAINRITSEG trial, run across 36 hospitals in France between March 2018 and June 2022, enrolled 98 people with newly diagnosed or relapsing EGPA who had recently reached remission — defined as a Birmingham Vasculitis Activity Score of 0 on a scale of 0 to 63 — after standard induction treatment [s1][s2]. It was a double-blind, double-dummy, superiority trial: each participant received an active drug and a matching placebo for the other, so neither patients nor doctors knew which maintenance they were on [s1].

Forty-nine people were assigned to 500 mg of intravenous rituximab every six months for 18 months (plus an azathioprine placebo), and 49 to daily oral azathioprine for 24 months (plus a rituximab placebo) [s1]. Both groups followed the same standardised steroid taper. The main question was how long people stayed in total remission across the 28-month study while taking 7.5 mg a day or less of prednisone — the dose below which steroid harms ease. Fourteen secondary measures tracked relapses and asthma or sinus flares [s1].

What it found

On the primary measure, the two drugs were statistically indistinguishable. Mean time in remission on 7.5 mg/d of prednisone or less was 91.1 weeks (95% confidence interval 80.9 to 101.2) with rituximab versus 96.0 weeks (85.6 to 106.5) with azathioprine — a non-significant difference (P=.38) [s1]. The share of participants who stayed in remission across the full 28 months at that steroid dose was 17 of 49 (34.7%) with rituximab and 11 of 49 (22.4%) with azathioprine, a gap that did not reach significance (relative risk 1.51; 95% CI 0.83 to 2.73; P=.18) [s1].

Vasculitis relapses were uncommon in both arms — 7 people (14.3%) on rituximab versus 9 (18.4%) on azathioprine — as were significant asthma or sinus exacerbations, affecting 16 (32.7%) and 19 (38.8%) respectively [s1]. Of the 98 enrolled, 92 (94%) completed the trial; their mean age was 59.0 years and 51% were women [s1].

The safety signal ran the other way. Severe infections were markedly more common with rituximab — 23 people (46.9%) versus 12 (24.5%) on azathioprine — driven mainly by severe COVID-19 during the pandemic years of the trial [s1]. One participant in the azathioprine group died of a SARS-CoV-2 infection before vaccines were available [s1].

How to read it

A double-blind, placebo-controlled, registered trial is the strongest design available for this question, and its answer is clear on its own terms: rituximab was not superior to azathioprine for sustaining steroid-sparing remission in EGPA [s1][s2]. That matters because rituximab is the costlier, more intensively monitored option, and the result removes any assumption that it is automatically the better maintenance choice.

Two cautions apply. First, "not superior" is not the same as "equivalent" — the trial was powered to detect rituximab winning, not to prove the two drugs interchangeable, and the point estimates modestly favoured azathioprine on time in remission while modestly favouring rituximab on the proportion holding remission [s1]. Second, the trial ran through the pandemic, which inflated the severe-infection count on rituximab specifically through COVID-19; how much that generalises to a vaccinated, post-pandemic setting is uncertain [s1]. EGPA is also rare, and 98 participants is a substantial cohort for the disease but still a small trial in absolute terms. For the wider regulatory backdrop on EGPA drugs, see our coverage of the avacopan decision.

What to watch

The open questions are whether a longer or larger trial would separate the two drugs, how the infection risk looks outside a pandemic, and where newer targeted biologics for eosinophilic disease fit against these established maintenance options. For now, the trial reframes the choice as one weighing cost, monitoring and infection risk rather than clear efficacy.

This article describes research and is not medical advice. Decisions about vasculitis treatment belong with a qualified clinician.